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1.
Virulence ; 15(1): 2350893, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38725096

ABSTRACT

Coxiella burnetii (C. burnetii) is the causative agent of Q fever, a zoonotic disease. Intracellular replication of C. burnetii requires the maturation of a phagolysosome-like compartment known as the replication permissive Coxiella-containing vacuole (CCV). Effector proteins secreted by the Dot/Icm secretion system are indispensable for maturation of a single large CCV by facilitating the fusion of promiscuous vesicles. However, the mechanisms of CCV maintenance and evasion of host cell clearance remain to be defined. Here, we show that C. burnetii secreted Coxiella vacuolar protein E (CvpE) contributes to CCV biogenesis by inducing lysosome-like vacuole (LLV) enlargement. LLV fission by tubulation and autolysosome degradation is impaired in CvpE-expressing cells. Subsequently, we found that CvpE suppresses lysosomal Ca2+ channel transient receptor potential channel mucolipin 1 (TRPML1) activity in an indirect manner, in which CvpE binds phosphatidylinositol 3-phosphate [PI(3)P] and perturbs PIKfyve activity in lysosomes. Finally, the agonist of TRPML1, ML-SA5, inhibits CCV biogenesis and C. burnetii replication. These results provide insight into the mechanisms of CCV maintenance by CvpE and suggest that the agonist of TRPML1 can be a novel potential treatment that does not rely on antibiotics for Q fever by enhancing Coxiella-containing vacuoles (CCVs) fission.


Subject(s)
Bacterial Proteins , Coxiella burnetii , Lysosomes , Phosphatidylinositol 3-Kinases , Phosphatidylinositol Phosphates , Transient Receptor Potential Channels , Vacuoles , Coxiella burnetii/metabolism , Coxiella burnetii/growth & development , Coxiella burnetii/genetics , Vacuoles/microbiology , Vacuoles/metabolism , Lysosomes/metabolism , Lysosomes/microbiology , Phosphatidylinositol Phosphates/metabolism , Humans , Bacterial Proteins/metabolism , Bacterial Proteins/genetics , Transient Receptor Potential Channels/metabolism , Transient Receptor Potential Channels/genetics , Phosphatidylinositol 3-Kinases/metabolism , Animals , Q Fever/microbiology , HeLa Cells , Host-Pathogen Interactions
2.
Vis Comput Ind Biomed Art ; 7(1): 9, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38647624

ABSTRACT

With recent advancements in robotic surgery, notable strides have been made in visual question answering (VQA). Existing VQA systems typically generate textual answers to questions but fail to indicate the location of the relevant content within the image. This limitation restricts the interpretative capacity of the VQA models and their ability to explore specific image regions. To address this issue, this study proposes a grounded VQA model for robotic surgery, capable of localizing a specific region during answer prediction. Drawing inspiration from prompt learning in language models, a dual-modality prompt model was developed to enhance precise multimodal information interactions. Specifically, two complementary prompters were introduced to effectively integrate visual and textual prompts into the encoding process of the model. A visual complementary prompter merges visual prompt knowledge with visual information features to guide accurate localization. The textual complementary prompter aligns visual information with textual prompt knowledge and textual information, guiding textual information towards a more accurate inference of the answer. Additionally, a multiple iterative fusion strategy was adopted for comprehensive answer reasoning, to ensure high-quality generation of textual and grounded answers. The experimental results validate the effectiveness of the model, demonstrating its superiority over existing methods on the EndoVis-18 and EndoVis-17 datasets.

3.
Small ; : e2400142, 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38676334

ABSTRACT

Complex temporal molecular signals play a pivotal role in the intricate biological pathways of living organisms, and cells exhibit the ability to transmit and receive information by intricately managing the temporal dynamics of their signaling molecules. Although biomimetic molecular networks are successfully engineered outside of cells, the capacity to precisely manipulate temporal behaviors remains limited. In this study, the catalysis activity of isothermal DNA polymerase (DNAP) through combined use of molecular dynamics simulation analysis and fluorescence assays is first characterized. DNAP-driven delay in signal strand release ranged from 100 to 102 min, which is achieved through new strategies including the introduction of primer overhangs, utilization of inhibitory reagents, and alteration of DNA template lengths. The results provide a deeper insight into the underlying mechanisms of temporal control DNAP-mediated primer extension and DNA strand displacement reactions. Then, the regulated DNAP catalysis reactions are applied in temporal modulation of downstream DNA-involved reactions, the establishment of dynamic molecular signals, and the generation of barcodes for multiplexed detection of target genes. The utility of DNAP-based signal delay as a dynamic DNA nanotechnology extends beyond theoretical concepts and achieves practical applications in the fields of cell-free synthetic biology and bionic sensing.

4.
Front Oncol ; 14: 1276526, 2024.
Article in English | MEDLINE | ID: mdl-38482209

ABSTRACT

Objectives: This study aimed to create and validate a radiomics nomogram for non-invasive preoperative Ki-67 expression level prediction in patients with bladder cancer (BCa) using contrast-enhanced CT radiomics features. Methods: A retrospective analysis of 135 patients was conducted, 79 of whom had high levels of Ki-67 expression and 56 of whom had low levels. For the dimensionality reduction analysis, the best features were chosen using the least absolute shrinkage selection operator and one-way analysis of variance. Then, a radiomics nomogram was created using multiple logistic regression analysis based on radiomics features and clinical independent risk factors. The performance of the model was assessed using the Akaike information criterion (AIC) value, the area under the curve (AUC) value, accuracy, sensitivity, and specificity. The clinical usefulness of the model was assessed using decision curve analysis (DCA). Results: Finally, to establish a radiomics nomogram, the best 5 features were chosen and integrated with the independent clinical risk factors (T stage) and Rad-score. This radiomics nomogram demonstrated significant correction and discriminating performance in both the training and validation sets, with an AUC of 0.836 and 0.887, respectively. This radiomics nomogram had the lowest AIC value (AIC = 103.16), which was considered to be the best model. When compared to clinical factor model and radiomics signature, DCA demonstrated the more value of the radiomics nomogram. Conclusion: Enhanced CT-based radiomics nomogram can better predict Ki-67 expression in BCa patients and can be used for prognosis assessment and clinical decision making.

5.
J Inflamm Res ; 17: 1607-1619, 2024.
Article in English | MEDLINE | ID: mdl-38495340

ABSTRACT

Metrnl, recently identified as an adipokine, is a secreted protein notably expressed in white adipose tissue, barrier tissues, and activated macrophages. This adipokine plays a pivotal role in counteracting obesity-induced insulin resistance. It enhances adipose tissue functionality by promoting adipocyte differentiation, activating metabolic pathways, and exerting anti-inflammatory effects. Extensive research has identified Metrnl as a key player in modulating inflammatory responses and as an integral regulator of muscle regeneration. These findings position Metrnl as a promising biomarker and potential therapeutic target in treating inflammation-associated pathologies. Despite this, the specific anti-inflammatory mechanisms of Metrnl in immune-mediated osteolysis and arthritis remain elusive, warranting further investigation. In this review, we will briefly elaborate on the role of Metrnl in anti-inflammation function in inflammation-related osteolysis, arthritis, and pathological bone resorption, which could facilitate Metrnl's clinical application as a novel therapeutic strategy to prevent bone loss. While the pathogenesis of elbow stiffness remains elusive, current literature suggests that Metrnl likely exerts a pivotal role in its development.

6.
Signal Transduct Target Ther ; 9(1): 69, 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38531869

ABSTRACT

The Orthopoxvirus genus, especially variola virus (VARV), monkeypox virus (MPXV), remains a significant public health threat worldwide. The development of therapeutic antibodies against orthopoxviruses is largely hampered by the high cost of antibody engineering and manufacturing processes. mRNA-encoded antibodies have emerged as a powerful and universal platform for rapid antibody production. Herein, by using the established lipid nanoparticle (LNP)-encapsulated mRNA platform, we constructed four mRNA combinations that encode monoclonal antibodies with broad neutralization activities against orthopoxviruses. In vivo characterization demonstrated that a single intravenous injection of each LNP-encapsulated mRNA antibody in mice resulted in the rapid production of neutralizing antibodies. More importantly, mRNA antibody treatments showed significant protection from weight loss and mortality in the vaccinia virus (VACV) lethal challenge mouse model, and a unique mRNA antibody cocktail, Mix2a, exhibited superior in vivo protection by targeting both intracellular mature virus (IMV)-form and extracellular enveloped virus (EEV)-form viruses. In summary, our results demonstrate the proof-of-concept production of orthopoxvirus antibodies via the LNP-mRNA platform, highlighting the great potential of tailored mRNA antibody combinations as a universal strategy to combat orthopoxvirus as well as other emerging viruses.


Subject(s)
Orthopoxvirus , Vaccinia , Animals , Mice , Combined Antibody Therapeutics , Vaccinia/prevention & control , Antibodies, Viral , Vaccinia virus/genetics
7.
Adv Sci (Weinh) ; 11(17): e2309624, 2024 May.
Article in English | MEDLINE | ID: mdl-38408124

ABSTRACT

Mild-heat photothermal antibacterial therapy avoids heat-induced damage to normal tissues but causes bacterial tolerance. The use of photothermal therapy in synergy with chemodynamic therapy is expected to address this issue. Herein, two pseudo-conjugated polymers PM123 with photothermal units and PFc with ferrocene (Fc) units are designed to co-assemble with DSPE-mPEG2000 into nanoparticle NPM123/Fc. NPM123/Fc under 1064 nm laser irradiation (NPM123/Fc+NIR-II) generates mild heat and additionally more toxic ∙OH from endogenous H2O2, displaying a strong synergistic photothermal and chemodynamic effect. NPM123/Fc+NIR-II gives >90% inhibition rates against MDR ESKAPE pathogens in vitro. Metabolomics analysis unveils that NPM123/Fc+NIR-II induces bacterial metabolic dysregulation including inhibited nucleic acid synthesis, disordered energy metabolism, enhanced oxidative stress, and elevated DNA damage. Further, NPM123/Fc+NIR-II possesses >90% bacteriostatic rates at infected wounds in mice, resulting in almost full recovery of infected wounds. Immunodetection and transcriptomics assays disclose that the therapeutic effect is mainly dependent on the inhibition of inflammatory reactions and the promotion of wound healing. What is more, thioketal bonds in NPM123/Fc are susceptible to ROS, making it degradable with highly favorable biosafety in vitro and in vivo. NPM123/Fc+NIR-II with a unique synergistic antibacterial strategy would be much less prone to select bacterial resistance and represent a promising antibiotics-alternative anti-infective measure.


Subject(s)
Anti-Bacterial Agents , Disease Models, Animal , Nanoparticles , Photothermal Therapy , Polymers , Wound Infection , Animals , Mice , Nanoparticles/chemistry , Polymers/chemistry , Polymers/pharmacology , Wound Infection/drug therapy , Anti-Bacterial Agents/pharmacology , Photothermal Therapy/methods
8.
Behav Sci (Basel) ; 14(1)2024 Jan 07.
Article in English | MEDLINE | ID: mdl-38247693

ABSTRACT

Flexibly and actively updating expectations based on feedback is crucial for navigating daily life. Previous research has shown that people with schizophrenia (PSZ) have difficulty adjusting their expectations. However, there are studies suggesting otherwise. To explore this further, we used a novel trial-based expectation updating paradigm called attribute amnesia. In the task, the participants needed to report the location of a target stimulus among distractors in pre-surprise trials. In the surprise trial, they were unexpectedly asked to report the identity of the target before reporting its location. Afterward, control trials were conducted whereby the participants were asked the same questions as in the surprise trial. Notably, the surprise trial and control trials were nearly identical, except that the participants expected to be asked about identity information in the control trials but not in the surprise trial. Thus, an improvement in identity reporting accuracy in the control trials in comparison with the surprise trial indicated active updating of expectations. In the current study, a total of 63 PSZ and 60 healthy control subjects (HCS) were enrolled. We found that both the PSZ and the HCS were unable to report information that they had fully attended to (i.e., identity) in the surprise trial. However, both groups showed a significant improvement in reporting identity information even in the first control trial. Critically, there was no significant difference in the magnitude of improvement between the two groups. The current findings indicate that PSZ have the ability to update their expectations as quickly and flexibly as HCS, at least in the context of the current task. The possible factors that might contribute to the discrepancy regarding expectation updating are discussed.

10.
J Psychiatr Res ; 169: 134-141, 2024 01.
Article in English | MEDLINE | ID: mdl-38039687

ABSTRACT

BACKGROUND: Patients with major depressive disorder (MDD) frequently present with sleep disturbances and cognitive impairment. The purpose of this study was to investigate whether cognitive impairment is more severe in MDD patients with insomnia, and the underlying neural mechanisms. METHODS: A total of 41 MDD patients with insomnia and 43 MDD patients without insomnia were recruited. We used functional near-infrared spectroscopy (fNIRS) to assess changes in oxyhemoglobin (Oxy-Hb) concentrations in the brain of patients while performing a verbal fluency task (VFT). Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI), cognitive function by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and severity of depression by the Hamilton Depression Scale (HAMD). RESULTS: Compared to MDD patients without insomnia, those with insomnia had lower scores on the RBANS total and immediate memory, visuospatial/constructional, and delayed memory subscales, as well as lower oxy-Hb concentrations in the bilateral dorsolateral prefrontal cortex (DLPFC) and bilateral medial prefrontal cortex (mPFC).Further correlation analysis showed that there was a significant correlation between the RBANS total score in all brain regions except left mPFC in MDD patients with insomnia(all p < 0.05). Further multiple linear regression showed that Oxy-Hb concentrations of left DLPFC were independently associated with RBANS total score. CONCLUSION: Our study suggests that MDD patients with insomnia have more cognitive impairment, which is associated with impaired frontal brain activity. Our findings may provide new insights to understand the underlying neural mechanisms of both disorders MDD patients and provide potential clinical value for developing treatment strategies for insomnia in MDD patients.


Subject(s)
Depressive Disorder, Major , Sleep Initiation and Maintenance Disorders , Humans , Depressive Disorder, Major/complications , Depressive Disorder, Major/diagnostic imaging , Spectroscopy, Near-Infrared/methods , Sleep Initiation and Maintenance Disorders/complications , Sleep Initiation and Maintenance Disorders/diagnostic imaging , Prefrontal Cortex/metabolism , Oxyhemoglobins/metabolism , Cognition
11.
J Psychiatr Res ; 169: 31-37, 2024 01.
Article in English | MEDLINE | ID: mdl-38000181

ABSTRACT

OBJECTIVE: Although studies have confirmed that working memory (WM) is impaired among adults with major depressive disorder (MDD), generalizing these neurocognitive impairments to adolescents with MDD would be tenuous. Therefore, separate studies for adolescents with MDD are needed. Relatively little is known about the neural processes associated with WM dysfunction in adolescents with MDD. Thus, we examined whether adolescents with MDD have abnormal brain activation patterns compared to healthy controls (HC) during WM tasks and whether it was possible to distinguish adolescents with MDD and HC based on mean oxy-hemoglobin (Oxy-Hb) changes. METHOD: A total of 87 adolescents with MDD and 63 HC were recruited. Functional near-infrared spectroscopy (fNIRS) was performed to monitor the concentrations of Oxy-Hb in the frontotemporal lobe while participants performed three WM tasks in order to examine WM impairments in adolescents with depression. RESULTS: The mean changes in Oxy-Hb concentrations in the left prefrontal cortex and right prefrontal cortex were higher among HC than among patients during the encoding and maintenance phase under each WM-load task. Machine learning was used to distinguish adolescents with MDD and HC based on Oxy-Hb changes, with a moderate area under the curve of 0.84. CONCLUSIONS: This study revealed WM defects in adolescents with MDD compared to HC based on mean Oxy-Hb changes, which can be valuable for distinguishing adolescents with MDD from HC.


Subject(s)
Depressive Disorder, Major , Adult , Humans , Adolescent , Memory, Short-Term/physiology , Spectroscopy, Near-Infrared/methods , Brain/metabolism , Prefrontal Cortex/metabolism , Oxyhemoglobins/metabolism
12.
Environ Int ; 183: 108402, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38150804

ABSTRACT

Choosing a suitable bioaerosol sampler for atmospheric microbial monitoring has been a challenge to researchers interested in environmental microbiology, especially during a pandemic. However, a comprehensive and integrated evaluation method to fully assess bioaerosol sampler performance is still lacking. Herein, we constructed a customized wind tunnel operated at 2-20 km/h wind speed to systematically and efficiently evaluate the performance of six frequently used samplers, where various aerosols, including Arizona test dust, bacterial spores, gram-positive and gram-negative bacteria, phages, and viruses, were generated. After 10 or 60 min of sampling, the physical and biological sampling efficiency and short or long-term sampling capabilities were determined by performing aerodynamic particle size analysis, live microbial culturing, and a qPCR assay. The results showed that AGI-30 and BioSampler impingers have good physical and biological sampling efficiencies for short-term sampling. However, their ability to capture aerosols at low concentrations is restricted. SASS 2300 and BSA-350 wet-wall cyclones had excellent enrichment ratios and high microbial cultivability in both short-term and long-term sampling; however, they were not suitable for quantitative studies of aerosols. Polycarbonate filter samplers showed outstanding performance in physical and long-term sampling but lacked the ability to maintain microbial activity, which can be improved by gelatin filter samplers. However, limitations remain for some fragile microorganisms, such as E. coli phage PhiX174 and coronavirus GX_P2V. In addition, the effects of wind speed and direction should be considered when sampling particles larger than 4 µm. This study provides an improved strategy and guidance for the characterization and selection of a bioaerosol sampler for better measurement and interpretation of collected ambient bioaerosols.


Subject(s)
Occupational Exposure , Occupational Exposure/analysis , Escherichia coli , Anti-Bacterial Agents/analysis , Environmental Monitoring/methods , Gram-Negative Bacteria , Gram-Positive Bacteria , Aerosols/analysis , Particle Size
14.
BMJ Open ; 13(12): e074129, 2023 12 14.
Article in English | MEDLINE | ID: mdl-38101854

ABSTRACT

INTRODUCTION: Adolescent depression has been shown to be associated with many devastating psychosocial outcomes. However, there are many barriers that may prevent depressed individuals from receiving specialised treatment. Virtual reality (VR) technology has shown promise as one avenue for overcoming these challenges. This study first aims to evaluate the effectiveness of VR intervention on adolescent depression symptoms, and second, to determine the intervention's underlying mechanism of effect using functional near-infrared spectroscopy (fNIRS). METHODS AND ANALYSIS: This is a single-centre, prospective, randomised controlled clinical trial. Sixty-six eligible adolescents aged 12-18 years with a diagnosis of depression will be randomised in a 1:1 ratio to either the VR treatment group or the conventional treatment group. All patients for both groups will receive usual treatment during a 4-week intervention period. In addition, patients randomised to VR treatment group (n=33) will complete three 20 min VR sessions including attention, executive function and relaxation training per week. Moreover, 33 healthy adolescents will be recruited as the general population. Primary outcome (ie, depressive symptoms) and secondary outcomes (ie, anxiety symptoms, executive function, treatment emergent symptoms, haemoglobin changes measured by fNIRS) will be collected at preintervention, immediately postintervention and at 4 weeks follow-up. The data assessor and analyst will be blinded to group membership. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Ethics Committee of Lishui Second People's Hospital. Written informed consent will be obtained for all participants. Results will be disseminated through peer-reviewed journals, national or international conference presentations, media outlets, the internet and various community activities. TRIAL REGISTRATION NUMBER: ChiCTR2300067747.


Subject(s)
Depression , Virtual Reality Exposure Therapy , Adolescent , Humans , Anxiety/prevention & control , Depression/psychology , Prospective Studies , Randomized Controlled Trials as Topic , Spectroscopy, Near-Infrared , Virtual Reality Exposure Therapy/methods , Child
15.
Gen Psychiatr ; 36(6): e101166, 2023.
Article in English | MEDLINE | ID: mdl-38155843

ABSTRACT

Background: Non-invasive brain stimulation has improved cognitive functions in patients with Alzheimer's disease (AD), and some studies suggest a close relationship between cognition and plasticity. However, the clinical benefits of transcranial direct current stimulation (tDCS) in patients still need to be evaluated. Aims: This study examined the role of tDCS in improving cognition and whether the improved cognition is related to altered cortical plasticity. Methods: 124 patients with AD were randomly assigned to active tDCS (n=63) or sham tDCS (n=61). The tDCS was applied at the dorsolateral prefrontal cortex for 30 treatment sessions across 6 weeks (5 days per week, 2 days off). The Mini-Mental State Examination and the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) were used for cognition evaluation at baseline, week 2 and week 6. The cortical plasticity was represented by motor-evoked potential (MEP) measured with an electromyogram. Results: The results showed that multiple courses of active tDCS can improve the cognitive functions of patients with AD, especially in the memory domain (word recall, recall of test instructions and word recognition). In addition, the damaged MEP level was enhanced following active treatment. In the active tDCS group, the improvements in ADAS-Cog total and subitem (word recall and word recognition) scores were negatively correlated with the enhancement of MEP. Conclusions: Our research indicates for the first time that twice-a-day tDCS may improve the cognitive function of patients with AD. This study also suggests that cognitive dysfunction may be related to impaired cortical plasticity, which warrants mechanistic investigations of the relationship between cognition and plasticity in the future. Trial registration number: ChiCTR1900021067.

16.
Environ Geochem Health ; 46(1): 19, 2023 Dec 26.
Article in English | MEDLINE | ID: mdl-38147168

ABSTRACT

Antimony (Sb) and arsenic (As) contamination in agricultural soil poses human health risks through agricultural products. Soil washing with degradable low molecular weight organic acids (LMWOAs) is an eco-friendly strategy to remediate agricultural soils. In this study, three eco-friendly LMWOAs, oxalic acid (OA), tartaric acid (TA), and citric acid (CA), were used to treat Sb and As co-contaminated agricultural soil from Xikuangshan mine area. The OA, TA, and CA washed out 18.4, 16.8, and 26.6% of Sb and 15.3, 19.9, and 23.8% of As from the agricultural soil, with CA being the most efficient reagent for the soil washing. These organic acids also led to pH decline and macronutrients losses. Fraction analysis using a sequential extraction procedure showed that the three organic acids targeted and decreased the specifically sorbed (F2) (by 19.3-37.6% and 2.41-23.5%), amorphous iron oxide associated (F3) (by 49.1-61.2% and 51.2-70.2%), and crystallized iron oxide associated (F4) (by 12.3-26.0% and 26.1-29.1%) Sb and As. The leachability of Sb and As, as well as their concentrations and bioconcentration factor (BCF) in vegetables reduced due to the soil washing. It demonstrated that the bioavailability of both the elements was decreased by the organic acids washing. The concentrations of Sb and As in typical vegetable species cultivated in CA washed soil were less than the threshold value for consumption safety, while those in OA and TA washed soils were still higher than the value, suggesting that only CA is a potential washing reagent in soil washing for Sb- and As-contaminated agricultural soil.


Subject(s)
Arsenic , Soil , Humans , Antimony , Biological Availability , Organic Chemicals , Oxalic Acid , Citric Acid
17.
Medicine (Baltimore) ; 102(46): e36149, 2023 Nov 17.
Article in English | MEDLINE | ID: mdl-37986284

ABSTRACT

Treatment of deformed pelvic and acetabular fractures is a considerable challenge for orthopedic surgeons. The aim of this study was to assess the availability of a three-dimensional (3D) printing model used in patients with inveterate pelvic and acetabular fractures by comparing 3D printing technology with conventional surgery. We conducted a retrospective review of patients with inveterate pelvic and acetabular fractures treated in our department between January 2008 and June 2020. The patients were divided into 2 groups according to their willingness. Perioperative data and clinical outcomes were compared to evaluate clinical efficacy. The t-test, Fisher exact test, and multivariable logistic regression analysis were conducted. A P value of .05 or less was considered to be statistically significant (two-tailed). Thirty-seven patients were enrolled in our study. Seventeen patients were divided into the case group treated by 3D printing model-assisted preoperative planning, and 20 patients were divided into the control group treated by conventional surgery. Patients treated with the 3D printing model had significantly shorter operation times, less blood loss, and shorter fluoroscopy times. Patients in the case group also showed better pain relief according to visual analog scale scores. However, the elevations in pelvis and hip joint functional outcomes were similar between the 2 groups, and no significant difference was shown in the radiological result. The usage of 3D printing techniques in patients with inveterate pelvic and acetabular fractures is of great importance in preoperative preparation and optimization of surgery but cannot improve postoperative function compared with conventional treatment.


Subject(s)
Fractures, Bone , Hip Fractures , Spinal Fractures , Surgery, Computer-Assisted , Humans , Fractures, Bone/surgery , Retrospective Studies , Fracture Fixation, Internal/methods , Surgery, Computer-Assisted/methods , Hip Fractures/surgery , Printing, Three-Dimensional , Treatment Outcome , Pelvis , Acetabulum/surgery , Acetabulum/injuries
18.
Exploration (Beijing) ; 3(3): 20220171, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37933384

ABSTRACT

Diffuse alveolar damage (DAD) triggers neutrophilic inflammation in damaged tissues of the lung, but little is known about the distinct roles of tissue structural cells in modulating the recruitment of neutrophils to damaged areas. Here, by combining single-cell and spatial transcriptomics, and using quantitative assays, we systematically analyze inflammatory cell states in a mouse model of DAD-induced neutrophilic inflammation after aerosolized intratracheal inoculation with ricin toxin. We show that homeostatic resident fibroblasts switch to a hyper-inflammatory state, and the subsequent occurrence of a CXCL1-CXCR2 chemokine axis between activated fibroblasts (AFib) as the signal sender and neutrophils as the signal receiver triggers further neutrophil recruitment. We also identify an anatomically localized inflamed niche (characterized by a close-knit spatial intercellular contact between recruited neutrophils and AFib) in peribronchial regions that facilitate the pulmonary inflammation outbreak. Our findings identify an intricate interplay between hyper-inflammatory fibroblasts and neutrophils and provide an overarching profile of dynamically changing inflammatory microenvironments during DAD progression.

19.
Virulence ; 14(1): 2271688, 2023 12.
Article in English | MEDLINE | ID: mdl-37848422

ABSTRACT

The emergence of antibiotic-resistant Aeromonas strains in clinical settings has presented an escalating burden on human and public health. The dissemination of antibiotic resistance in Aeromonas is predominantly facilitated by chromosome-borne accessory genetic elements, although the existing literature on this subject remains limited. Hence, the primary objective of this study is to comprehensively investigate the genomic characteristics of chromosome-borne accessory genetic elements in Aeromonas. Moreover, the study aims to uncover novel genetic environments associated with antibiotic resistance on these elements. Aeromonas were screened from nonduplicated strains collected from two tertiary hospitals in China. Complete sequencing and population genetics analysis were performed. BLAST analysis was employed to identify related elements. All newly identified elements were subjected to detailed sequence annotation, dissection, and comparison. We identified and newly designated 19 chromosomal elements, including 18 integrative and mobilizable elements (IMEs) that could be classified into four categories: Tn6737-related, Tn6836-related, Tn6840-related, and Tn6844a-related IMEs. Each class exhibited a distinct pattern in the types of resistance genes carried by the IMEs. Several novel antibiotic resistance genetic environments were uncovered in these elements. Notably, we report the first identification of the blaOXA-10 gene and blaVEB-1 gene in clinical A. veronii genome, the first presence of a tetA(E)-tetR(E) resistance gene environment within the backbone region in IMEs, and a new mcr-3.15 resistance gene environment. The implications of these findings are substantial, as they provide new insights into the evolution, structure, and dissemination of chromosomal-borne accessory elements.


Subject(s)
Aeromonas , Humans , Aeromonas/genetics , Drug Resistance, Microbial , Anti-Bacterial Agents/pharmacology , Chromosomes , China
20.
Eur J Med Res ; 28(1): 440, 2023 Oct 17.
Article in English | MEDLINE | ID: mdl-37848987

ABSTRACT

BACKGROUND: Renal cell carcinoma (RCC) accounts for approximately 2-3% of all adult malignancies. Clear cell renal cell carcinoma (ccRCC), which comprises 70-80% of all RCC cases, is the most common histological subtype. METHODS: ccRCC transcriptome data and clinical information were downloaded from the TCGA database. We used the TCGA and GEPIA databases to analyze relative expression of BMP1 in various types of human cancer. GEPIA was used to perform survival analysis for BMP1 in various cancer types. Upstream binding miRNAs of BMP1 were obtained through several important target gene prediction tools. StarBase was used to predict candidate miRNAs that may bind to BMP1 and candidate lncRNAs that may bind to hsa-miR-532-3p. We analyzed the association between expression of BMP1 and immune cell infiltration levels in ccRCC using the TIMER website. The relationship between BMP1 expression levels and immune checkpoint expression levels was also investigated. RESULTS: BMP1 was upregulated in GBM, HNSC, KIRC, KIRP and STAD and downregulated in KICH and PRAD. Combined with OS and DFS, BMP1 can be used as a biomarker for poor prognosis among patients with KIRC. Through expression analysis, survival analysis and correlation analysis, LINC00685, SLC16A1-AS1, PVT1, VPS9D1-AS1, SNHG15 and the CCDC18-AS1/hsa-miR-532-3p/BMP1 axis were established as the most potential upstream ncRNA-related pathways of BMP1 in ccRCC. Furthermore, we found that BMP1 levels correlated significantly positively with tumor immune cell infiltration, biomarkers of immune cells, and immune checkpoint expression. CONCLUSION: Our results demonstrate that ncRNA-mediated high expression of BMP1 is associated with poor prognosis and tumor immune infiltration in ccRCC.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , MicroRNAs , RNA, Long Noncoding , Humans , Bone Morphogenetic Protein 1 , Carcinoma, Renal Cell/genetics , Kidney Neoplasms/genetics , MicroRNAs/genetics , RNA, Long Noncoding/genetics , Up-Regulation/genetics
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